Headache and Migraine: Pubertal Parameter and Hormone Predictors PROJECT SUMMARY Headache is a highly prevalent health problem, which often first occurs in childhood. The prevalence of childhood headache increases in both sexes until early adolescence, when the frequency in girls exceeds that in boys. The increase of headache in females may be a consequence of pubertal development, as estradiol is known to be associated with increased risk of migraine and also a driver of pubertal development. During the female ovulatory cycle, hormone changes, namely fluctuations in estradiol, can influence migraine. The puberty cohort study of the Breast Cancer and the Environment Research Program followed over 1200 girls from Cincinnati, New York City and the San Francisco Bay Area for 10 years, beginning at age 6-8 years, with yearly questionnaire data collection and annual or semi-annual pubertal staging, anthropometry examinations and biospecimen collection. The final questionnaire included items about migraine and headache, used to classify girls as having severe headaches, migraine, possible menstrual migraine and definite menstrual migraine. We propose to use the multiple research resources of this cohort to address the following Aims: Aim 1: Using previously collected data from a large cohort of adolescent girls, establish the prevalence of severe headaches and migraine among 761 girls at age 12 ? 16 years by demographic, anthropometric, and behavioral characteristics and determine if severe headaches and migraine are associated with age at pubertal parameters, such as age at thelarche, pubarche, menarche, age at peak height velocity and peak height velocity. Aim 2: In a subset of the cohort (N=220) with both headache and migraine data and repeated measurements of serum hormone concentrations at various time points during pubertal development, determine if levels of estradiol (E2), androstendione (DHEAS), estrone (E1) and testosterone (T) are associated with later headaches and migraine. We hypothesize that migraine headache will be associated with earlier age at thelarche, pubarche, menarche, peak height velocity and greater peak height. We also hypothesize that higher estradiol (E2) levels at thelarche will be associated with headache and migraine. The contribution of this study will be the first assessment of the association between severe headaches and migraine in adolescent girls and age at thelarche and peak height velocity. Although estradiol is widely recognized as being the primary hormone driving menarche, and menarche is known to increase the prevalence of severe headache and migraine, we know of no study that has examined whether earlier estradiol-driven events, such as thelarche and peak height velocity, may also be related. Our sub-cohort, with longitudinal measures of serum hormones around the time of thelarche, provides an unique opportunity to study whether early hormone status is related. When mechanisms responsible for these conditions are better understood, more targeted therapies and interventions to treat these conditions can be developed, improving quality of life, decreasing health care costs, and alleviating absenteeism and presenteeism in young women.